There is considerable literature relating to bioaffinity separation techniques based upon the principle that a column, operated generally on the principles of a chromatographic separation, whereby a sorbent to which a particular component of a mixture of bioactive components has affinity may be used for the separation of that component and its recovery.
For the purposes of this description, when we refer to the principles of chromatography or chromatographic separations generally, we intend to denote those separation techniques which involve selective retention on the active material of the column of a particular component of a mixture or the retardation of migration through the column of a particular component or of particular components so that, upon elution by an eluant, the concentration of a component to be separated in the eluate at a particular time during the progress of elution is substantially greater than the concentration of that component in the original mixture.
The principle has been applied to the separation of bioactive materials. The term "bioactive material" or "bioactive component" is here used to refer to a molecular species in a mixture which is active biologically in some fashion. It may be, for example, a hormone, a pharmaceutically active compound, a species capable of cell binding or a substance active in molecular biology or genetics or produced by molecular biology, cloning or hybridization techniques. It may also be a dietary supplement, a fragrance or other cosmetics component, or a substance having laboratory, testing or analytical interest.
A number of patents have been issued which utilize the principles of bioaffinity separation and which disclose various biospecific sorbents which may be used in the principles of this invention.
For example, U.S. Pat. No. 4,661,408 describes the use of chromium dioxide particles as support in bioaffinity separations while U.S. Pat. No. 4,554,088 describes bioaffinity separations utilizing magnetic particles.
A quantitative screening protocol for the assay of tumor globulin utilizes a biospecific sorbent in U.S. Pat. No. 4,656,025 and U.S. Pat. No. 4,655,918 describes the use of bioreactors in the microbiological cleaning of waste water (see also U.S. Pat. No. 4,505,820).
Electrical principles can also be used to control migration in columns containing specific sorbents (See U.S. Pat. No. 4,642,169) and complex apparatus can also be provided to utilize the principles (see U.S. Pat. No. 4,597,947).
Other related patents which consider the use of chromatography for the separation of biological substances include U.S. Pat. Nos. 4,431,544; 4,375,401; 4,289,628; 4,283,199; 4,278,594; 4,210,580; 4,067,825; 4,062,831; 3,994,805; 3,965,130; 3,853,765; and 3,784,467.
It is desirable to increase the selectivity and efficiency of bioaffinity separations and this is the problem attacked by the present invention.